Effects Of Antibiotic Therapy On Intestinal Flora And Its Related Immune Function In Patients With Prosthetic Joint Infection

Part 1 Effects of vancomycin treatment on intestinal flora and immune function of SD rats with prosthetic joint infectionObjective: Patients with prosthetic joint infections often need a long-course antibiotic treatment,which can have a significant impact their intestinal flora.Normal intestinal flora structure is closely related to partial host immune function.However,the effect of different courses of vancomycin treatment on PJI patients’ intestinal flora and its related immune function remains unclear.The purpose of this study was to analyze the effects of different courses of vancomycin treatment on intestinal flora and its related immune functions of SD rats with PJI.Materials and methods: 15 female SD rats(PJI animal model)were randomly divided into three groups.The SD rats in groupⅠwere treated with 1% vancomycin solution(10ml/kg·d)for 6 weeks,the SD rats in groupⅡwere treated with 1% vancomycin solution(10ml/kg·d)for 12 weeks and the SD rats in groupⅢ were treated as same as the former groups only with the solvent(7% Tween-80 solution with 3% ethyl alcohol)for 12 weeks.Collecting feces samples,whole blood samples and serum samples at three pre-set time points.The 16 s r DNA high-throughput sequencing technique was used to analyze and compare the information of the intestinal flora of PJI animal models.Flow cytometry was used to analyze the level of T lymphocyte(CD3+、CD4+、CD8+)in all peripheral blood samples of PJI animal models and enzyme-linked immunosorbent assay was used to detect the concentration of Ig G,Reg3γ and GM-CSF in all serum samples of PJI animal models.Results: Before vancomycin treatment,there were no statistically significant differences in OTU,Chao,Ace,Shannon and other indicators of intestinal flora in the three groups of PJI animal models(P>0.05).After 6 weeks of vancomycin treatment,there was a significant difference in the structure of intestinal flora at the both level of Phylum and Family between groupⅠand Ⅲ(P<0.05),the proportion of Bacteroidetes decreased significantly.After 12 weeks of vancomycin treatment,there was a significant difference in the structure of intestinal flora at the both level of Phylum and Family between groupⅡand Ⅲ(P<0.05),the proportion of Bacteroidetes decreased significantly,however,the proportion of Proteobacteria and Enterobacteriaceae increased significantly.There were significant differences in OTU,Chao index,Ace index,the structure of intestinal flora,the level of T lymphocyte in peripheral blood and so on between group Ⅰand Ⅱ after the different courses vancomycin treatment.Conclusions: Vancomycin can significantly affect the intestinal flora and its related immune function of PJI animal models.The effect of long-course vancomycin treatment on intestinal flora and its related immune function was significantly greater than short-course vancomycin treatment.Part 2 Effects of antibiotic therapy on intestinal flora and immune function of patients with prosthetic joint infectionObjective: PJI patients often need long-term antibiotic treatment during the interval time between two stages and antibiotic treatment can significantly affect the patients’ intestinal flora.Normal intestinal flora structure is closely related to some immune functions of mankind.However,the effect of different courses of antibiotic therapy on PJI patients’ intestinal flora and its related immune funcion is still unclear.The aim of this study was to analyze the effect of different courses of antibiotic therapy on PJI patients’ intestinal flora and its related immune function.Materials and methods: A prospective study included 14 patients who were definitely diagnosed as PJI and whose pathogenic microorganisms were Gram-positive bacteria from May 2018 to May 2019.According to the principle of randomization,the patients were divided into two groups: short-course antibiotic treatment group(group I)and long course antibiotic treatment group(group II).Fecal samples and serum samples were collected before and after antibiotic treatment.16 S r DNA high-throughput sequencing technology was used to analyse and compare the information of PJI patients’ intestinal flora and enzyme-linked immunosorbent assay was used to detect the concentration of Ig G,Reg3γand TNF-αin all serum samples of PJI patients.Results: There was no significant difference in OTU,Chao,Ace,Shannon and other indicators of intestinal flora between the two groups before antibiotics treatment(P > 0.05).After 6 weeks of antibiotic treatment,the OTU,Chao value,Ace value,Shannon value and Simpson value of PJI patients’ intestinal flora in group I decreased significantly compared with those before antibiotic treatment(P<0.05).Meanwhile,the structure of PJI patients’ intestinal flora changed significantly.At the level of phylum,the proportion of Bacteroideae decreased significantly(P<0.05)and at the level of Family,the proportion of Bacteroideae decreased significantly(P<0.05).After 12 weeks of antibiotic treatment,the OTU value,Chao value,Ace value,Shannon value and Simpson value of PJI patients’ intestinal flora in group II decreased significantly compared with those before treatment(P<0.05).At the same time,the structure of PJI patients’ intestinal flora in group II changed significantly.At the level of phylum,the proportion of Bacteroides decreased significantly,and the proportion of Proteobacteria increased significantly(P < 0.05).At the level of Family,the proportion of Bacteriaceae decreased significantly and that of Enterobacteriaceae increased significantly(P < 0.05).After antibiotic treatment,the OTU value of patients’ intestinal flora decreased significantly and Simpson value of patients’ intestinal flora increased significantly in group II compared with group I(P < 0.05).At the same time,the structure of PJI patients’ intestinal flora in group II was significantly different from those in group I.At the level of phylum,the proportion of Bacteroides decreased significantly(P < 0.05).At the level of Family,the proportion of Bacteroides decreased significantly,however,the proportion of Enterobacteriaceae increased significantly.At the end of antibiotic therapy,the concentration of Reg3γand TNF-αin PJI patients(in group Ⅱ)were significant higher than those in another group.Conclusions: Antibiotics can significantly affect PJI patients’ intestinal flora and its related immune function.The effect of long-course antibiotic therapy on PJI patients’ intestinal flora and its related immune function was significantly greater than short-course antibiotic treatment.